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  1. Diabetes-associated macrovasculopathy: pathophysiology and pathogenesis
    Rahman S, Rahman T, Ismail AA, Rashid AR
    Diabetes Obes Metab, 2007 Nov;9(6):767-80.
    PMID: 17924861 DOI: 10.1111/j.1463-1326.2006.00655.x
    The complications associated with diabetic vasculopathy are commonly grouped into two categories: microvascular and macrovascular complications. In diabetes, macrovascular disease is the commonest cause of mortality and morbidity and is responsible for high incidence of vascular diseases such as stroke, myocardial infarction and peripheral vascular diseases. Macrovascular diseases are traditionally thought of as due to underlying obstructive atherosclerotic diseases affecting major arteries. Pathological changes of major blood vessels leading to functional and structural abnormalities in diabetic vessels include endothelial dysfunction, reduced vascular compliance and atherosclerosis. Besides, advanced glycation end product formation interacts with specific receptors that lead to overexpression of a range of cytokines. Haemodynamic pathways are activated in diabetes and are possibly amplified by concomitant systemic hypertension. Apart from these, hyperglycaemia, non-enzymatic glycosylation, lipid modulation, alteration of vasculature and growth factors activation contribute to development of diabetic vasculopathy. This review focuses on pathophysiology and pathogenesis of diabetes-associated macrovasculopathy.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  2. A study of the factors related to intima-media thickness of the common carotid artery amongst rural middle age individuals in Hospital Universiti Sains Malaysia
    Yunus R, Ariff AR, Shuaib IL, Jelani AM, Alias NA, Abdullah J, et al.
    Southeast Asian J. Trop. Med. Public Health, 2006 Jul;37(4):806-11.
    PMID: 17121310
    There is very little data regarding the factors related to intima-media thickness (IMT) of the common carotid artery in normal individuals in those with non-insulin diabetes mellitus and perimenopausal women in Southeast Asian countries. Ultrasound imaging evaluating the carotid artery IMT in those with diabetes and those on hormone replacement therapy (HRT) was performed beginning in August 2000 for a period of nearly two years at the Department of Radiology, Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia. A total of 153 participants were included. Significant differences between the women on HRT and not on HRT were IMT and systolic blood pressure. When comparing those with non-insulin dependent diabetes mellitus (NIDDM) and normal individuals, the significant differences were IMT, total cholesterol level, systolic blood pressure and diastolic blood pressure. IMT was high in those with NIDDM but not in those on HRT. Both those with NIDDM and those on HRT had associated dyslipidemia and systolic hypertension.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology*
  3. Fulltext Diabetic control among NIDDM patients in urban and rural areas in Malaysia
    Ruzita AT, Osman A, Fatimah A, Khalid BA
    Med J Malaysia, 1996 Mar;51(1):48-51.
    PMID: 10967979
    Sixty three and fifty nine non-insulin dependent diabetes mellitus (NIDDM) patients in rural (land resettlement scheme) and urban areas respectively were studied to determine factors associated with diabetic control. The anthropometric and metabolic data (HbA1 and fructosamine levels) were analysed. After adjusting for gender, age, body mass index (BMI) and food intake, the fructosamine level which correlates with short term diabetic control, was significantly lower among patients in urban areas compared to patients in rural areas (p < 0.05). However, for longer term diabetic control (HbA1 level) the difference was not statistically significant (p > 0.05). The socio-economic status, level of education, BMI and types of food did not correlate with diabetic control in either group of patients. More diabetes education is needed together with socio-economic development and changes in lifestyles to enhance compliance towards health and dietary regimens and to achieve better metabolic control.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  4. Fulltext The internal realities of individuals with type 2 diabetes  - a functional framework of self-management practices via Grounded Theory approach
    Swarna Nantha Y, Haque S, Paul Chelliah AA
    PLoS One, 2019;14(11):e0225534.
    PMID: 31770421 DOI: 10.1371/journal.pone.0225534
    BACKGROUND: An upward trend is observed in the prevalence of Type 2 diabetes (T2D) in South-East Asian and Western Pacific regions. These patterns incur a costly health burden to developing nations around the world. A clear understanding of the mechanics behind self-management practices of T2D patients might help overcome this impasse. This information can help unlock specific problem areas that warrant specific intervention. We aim to uncover prevailing T2D self-management habits and its deviations from optimal behaviour.

    METHODS: We adopted a Grounded Theory approach to guide in-depth interviews (IDI) with T2D patients and healthcare providers (HCP) at a regional primary care clinic in Malaysia. Twenty-four T2D patients and 10 HCPs were recruited through purposive sampling to examine their inner psychological narratives related to self-management practices. 2 focus group discussions (FGD) were conducted as a part of the data triangulation process.

    RESULTS: A functional framework for self-management practices in T2D patients was developed. Self-management behavior was characterized by 2 major processes- 1) helpful and, 2) unhelpful practices. Self-efficacy, taking responsibility and being rational define helpful behaviour in these patients. On the other hand, unhelpful traits (neglect, poor restraint, and experimentation) often trigger violations with regards to medication compliance and therapeutic lifestyle changes.

    CONCLUSIONS: We outlined a roadmap that navigates through the positive and negative mindset in relation to self-management practices of T2D patients. These results highlight the importance of devising individualized strategies by taking into account the personal challenges, emotions, and motivations that define the inner self of the patient.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  5. Brown/Beige adipose tissues and the emerging role of their secretory factors in improving metabolic health: The batokines
    Ahmad B, Vohra MS, Saleemi MA, Serpell CJ, Fong IL, Wong EH
    Biochimie, 2021 May;184:26-39.
    PMID: 33548390 DOI: 10.1016/j.biochi.2021.01.015
    Brown and beige adipose tissues are the primary sites for adaptive non-shivering thermogenesis. Although they have been known principally for their thermogenic effects, in recent years, it has emerged that, just like white adipose tissue (WAT), brown and beige adipose tissues also play an important role in the regulation of metabolic health through secretion of various brown adipokines (batokines) in response to various physiological cues. These secreted batokines target distant organs and tissues such as the liver, heart, skeletal muscles, brain, WAT, and perform various local and systemic functions in an autocrine, paracrine, or endocrine manner. Brown and beige adipose tissues are therefore now receiving increasing levels of attention with respect to their effects on various other organs and tissues. Identification of novel secreted factors by these tissues may help in the discovery of drug candidates for the treatment of various metabolic disorders such as obesity, type-2 diabetes, skeletal deformities, cardiovascular diseases, dyslipidemia. In this review, we comprehensively describe the emerging secretory role of brown/beige adipose tissues and the metabolic effects of various brown/beige adipose tissues secreted factors on other organs and tissues in endocrine/paracrine manners, and as well as on brown/beige adipose tissue itself in an autocrine manner. This will provide insights into understanding the potential secretory role of brown/beige adipose tissues in improving metabolic health.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  6. Metabolic Syndrome and Its Effect on the Brain: Possible Mechanism
    Arshad N', Lin TS, Yahaya MF
    CNS Neurol Disord Drug Targets, 2018;17(8):595-603.
    PMID: 30047340 DOI: 10.2174/1871527317666180724143258
    BACKGROUND & OBJECTIVE: Metabolic syndrome (MetS) is an interconnected group of physiological, biochemical, clinical and metabolic factors that directly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) and mortality. Rising evidence suggests that MetS plays a significant role in the progression of Alzheimer's disease and other neurodegenerative diseases. Nonetheless, the factors linking this association has not yet been elucidated. As we are facing an increasing incidence of obesity and T2DM in all stages of life, understanding the association of MetS and neurodegenerative diseases is crucial to lessen the burden of the disease.

    CONCLUSION: In this review, we will discuss the possible mechanisms which may relate the association between MetS and cognitive decline which include vascular damages, elevation of reactive oxygen species (ROS), insulin resistance and low-grade inflammation.

    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  7. Fulltext Investigating the association of CD36 gene polymorphisms (rs1761667 and rs1527483) with T2DM and dyslipidemia: Statistical analysis, machine learning based prediction, and meta-analysis
    Hatmal MM, Alshaer W, Mahmoud IS, Al-Hatamleh MAI, Al-Ameer HJ, Abuyaman O, et al.
    PLoS One, 2021;16(10):e0257857.
    PMID: 34648514 DOI: 10.1371/journal.pone.0257857
    CD36 (cluster of differentiation 36) is a membrane protein involved in lipid metabolism and has been linked to pathological conditions associated with metabolic disorders, such as diabetes and dyslipidemia. A case-control study was conducted and included 177 patients with type-2 diabetes mellitus (T2DM) and 173 control subjects to study the involvement of CD36 gene rs1761667 (G>A) and rs1527483 (C>T) polymorphisms in the pathogenesis of T2DM and dyslipidemia among Jordanian population. Lipid profile, blood sugar, gender and age were measured and recorded. Also, genotyping analysis for both polymorphisms was performed. Following statistical analysis, 10 different neural networks and machine learning (ML) tools were used to predict subjects with diabetes or dyslipidemia. Towards further understanding of the role of CD36 protein and gene in T2DM and dyslipidemia, a protein-protein interaction network and meta-analysis were carried out. For both polymorphisms, the genotypic frequencies were not significantly different between the two groups (p > 0.05). On the other hand, some ML tools like multilayer perceptron gave high prediction accuracy (≥ 0.75) and Cohen's kappa (κ) (≥ 0.5). Interestingly, in K-star tool, the accuracy and Cohen's κ values were enhanced by including the genotyping results as inputs (0.73 and 0.46, respectively, compared to 0.67 and 0.34 without including them). This study confirmed, for the first time, that there is no association between CD36 polymorphisms and T2DM or dyslipidemia among Jordanian population. Prediction of T2DM and dyslipidemia, using these extensive ML tools and based on such input data, is a promising approach for developing diagnostic and prognostic prediction models for a wide spectrum of diseases, especially based on large medical databases.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  8. Fulltext Genetic Analysis of the Atrial Natriuretic Peptide Gene Polymorphisms among Essential Hypertensive Patients in Malaysia
    Ghodsian N, Ismail P, Ahmadloo S, Eskandarian N, Etemad A
    Biomed Res Int, 2016;2016:6712529.
    PMID: 27413750 DOI: 10.1155/2016/6712529
    Background. Atrial natriuretic peptide (ANP) considerably influences blood pressure regulation through water and sodium homoeostasis. Several of the studies have utilized anonymous genetic polymorphic markers and made inconsequent claims about the ANP relevant disorders. Thus, we screened Insertion/Deletion (ID) and G191A polymorphisms of ANP to discover sequence variations with potential functional significance and to specify the linkage disequilibrium pattern between polymorphisms. The relationships of detected polymorphisms with EH with or without Type 2 Diabetes Mellitus (T2DM) status were tested subsequently. Method. ANP gene polymorphisms (I/D and A191G) were specified utilizing mutagenically separated Polymerase Chain Reaction (PCR) in 320 subjects including 163 EH case subjects and 157 controls. Result. This case-control study discovered a significant association between I/D polymorphisms of ANP gene in EH patient without T2DM. However, the study determined no association between G191A polymorphisms of ANP in EH with or without T2DM. In addition, sociodemographic factors in the case and healthy subjects exhibited strong differences (P < 0.05). Conclusion. As a risk factor, ANP gene polymorphisms may affect hypertension. Despite the small sample size in this study, it is the first research assessing the ANP gene polymorphisms in both EH and T2DM patients among Malaysian population.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  9. Fulltext Performance of the Malay Audit of Diabetes Dependent Quality of Life-18 and Associates of Quality of Life among Patients with Type 2 Diabetes Mellitus from Major Ethnic Groups of Malaysia
    Daher AM, AlMashoor SH, Winn T
    PLoS One, 2016;11(10):e0163701.
    PMID: 27695086 DOI: 10.1371/journal.pone.0163701
    INTRODUCTION: Diabetes Mellitus (DM) is notorious for its metabolic effect, acute and chronic complications and impact on Quality of Life (QoL). Successful intervention to improve QoL necessitates a valid and reliable measurement tool to identify areas of concern to patients with diabetes.
    OBJECTIVES: To (1) assess the factor structure of the Malay Audit of Diabetes Dependent Quality of Life-18 (ADDQoL-18) questionnaire; (2) determine the impact of DM on QoL; and (3) identify areas of concern to patients with type 2 DM from three major ethnic groups in Malaysia.
    METHODS: Data was obtained from a cross sectional study involving 256 patients with type 2 DM attending the diabetes clinic of the National University of Malaysia Medical Centre. The Malay version of ADDQoL-18 survey was translated from its English version according to standard guidelines and administered by a trained research assistant. Exploratory Factor Analysis (EFA) with oblimin rotation was used to determine factor structure of the data. Confirmatory Factor Analysis (CFA) was used to confirm the factor structure. Hierarchical liner regression was used to determine factors associated with QoL.
    RESULTS: Unforced factor solution yielded two factors for the whole sample. Forced one factor solution was ascertained for the whole sample and for each ethnic group. Loadings ranged between 0.588 and 0.949. Reliability coefficients were all higher than 0.955. CFA showed that the two factor model had better fit statistics. QoL was associated with the use of insulin and desired glycaemic control, longer diabetes duration, worry about diabetes, and diabetes complications.
    CONCLUSIONS: The Malay ADDQoL-18 is a valid tool to be used among patients with diabetes from different ethnic groups in Malaysia. The use of insulin to achieve desired glycaemic control had more negative impact on QoL than the use of tablets and/or dietary changes.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  10. The associations between diabetes distress and self-efficacy, medication adherence, self-care activities and disease control depend on the way diabetes distress is measured: Comparing the DDS-17, DDS-2 and the PAID-5
    Chew BH, Vos RC, Pouwer F, Rutten GEHM
    Diabetes Res Clin Pract, 2018 Aug;142:74-84.
    PMID: 29802952 DOI: 10.1016/j.diabres.2018.05.021
    AIMS: To examine whether diabetes distress (DD), when measured by three different instruments, was associated differently with self-efficacy, self-care activity, medication adherence and disease control in people with Type 2 diabetes mellitus.
    METHODS: A cross-sectional study in three health clinics. DD was assessed with the 17-item Diabetes Distress Scale, the 2-item DDS-2 (DDS-2) and the 5-item Problem Areas in Diabetes Scale (PAID-5). Dependent variables included self-efficacy, self-care activities, medication adherence, HbA1c, systolic and diastolic blood pressure (SBP, DBP). Multiple linear and logistic regression were used in analyses.
    RESULTS: In total 338 participants (56% women), with a mean age of 61 years and diabetes duration of 9.8 years, were included. DDS-2 was an independent determinant of SBP (β = 1.89, 95% CI 0.14, 3.64), DBP (β = 1.19, 95% CI 0.16, 2.21) and blood pressure target (OR = 2.09, 95% CI 1.12, 3.83). PAID-5 was an independent determinant of medication adherence (adjusted β = -0.05, 95% CI -0.08, -0.01) and self-care activities (OR = 0.50, 95% CI 0.26, 0.99).
    CONCLUSIONS: Associations of DD with important aspects of diabetes care are substantially influenced by confounders and depend on the way DD is measured. Our findings call for a judicious use of different DD measures in clinical practice and research. The study is registered on ClinicalTrials.gov (NCT02730754).
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  11. Emerging Role of Adipocytokines in Type 2 Diabetes as Mediators of Insulin Resistance and Cardiovascular Disease
    Jaganathan R, Ravindran R, Dhanasekaran S
    Can J Diabetes, 2018 Aug;42(4):446-456.e1.
    PMID: 29229313 DOI: 10.1016/j.jcjd.2017.10.040
    Adipose tissue is an enormously active endocrine organ, secreting various hormones, such as adiponectin, leptin, resistin and visfatin, together with classical cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). All these adipocytokines play significant roles in the regulation of energy metabolism, glucose and lipid metabolism, reproduction, cardiovascular function and immunity. Adipocytokines are significantly regulated by nutritional status and can directly influence other organ systems, including brain, liver and skeletal muscle. Adiponectin plays a key role as an anti-inflammatory hormone. Upregulated expression of resistin, vaspin, apelin and TNF-α plays a significant role in induction of insulin resistance linked with obesity and type 2 diabetes. Ghrelin, the circulating peptide, has been found to stimulate appetite and regulate energy balance. Thus, it can be considered 1 of the candidate genes for obesity and type 2 diabetes. Omentin is a novel adipokine produced by visceral adipose tissue. Circulating levels of omentin are decreased in insulin-resistant states, for example, in obesity and diabetes. IL-6 plays a vital role in regulating the accumulation of lipids intramyocardially. Based on the biologic relevance of these adipocytokines, they can no longer be considered as energy storage sites alone but must also be considered in metabolic control. Hence, the present review summarizes the regulatory roles of adipocytokines in diabetes linked with obesity.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  12. Discovery of α-Glucosidase Inhibitors from Marine Microorganisms: Optimization of Culture Conditions and Medium Composition
    Trang NTH, Tang DYY, Chew KW, Linh NT, Hoang LT, Cuong NT, et al.
    Mol Biotechnol, 2021 Nov;63(11):1004-1015.
    PMID: 34185249 DOI: 10.1007/s12033-021-00362-3
    Various studies showed that the suppression of α-glucosidase activity can impede the glucose absorption in our body, and therefore, it can be used to treat type 2 diabetes. Hence, the compounds with anti-α-glucosidase have gained considerable attention because of their potential application in diabetes treatment. In previous literature studies, these anti-α-glucosidase compounds were extracted from plants and fungus. Less studies are being conducted to identify the anti-α-glucosidase compounds in the microbial community. In this study, 23 marine bacterial strains were screened for their potential to suppress the α-glucosidase activity. The highest inhibitory activity was exhibited by isolated L06 which was identified as Oceanimonas smirnovii EBL6. The cultivation conditions, such as temperature and pH, were optimized to increase the production of α-glucosidase inhibitors by Oceanimonas smirnovii EBL6 strain. The result findings showed that the highest yield of α-glucosidase inhibitors can be obtained at the culture time of 120 h, fermentation temperature of 30 °C, and pH 4.6. Under these conditions, the inhibitory activity of α-glucosidase can reach 81%. The IC50 of n-butanol extract was 13.89 μg/ml, while standard acarbose was 31.16 μg/ml. Overall, these findings suggest that Oceanimonas smirnovii produces α-glucosidase inhibitors and could been applied in the biochemical and medicinal fields in the future.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  13. Fulltext Action of Phytochemicals on Insulin Signaling Pathways Accelerating Glucose Transporter (GLUT4) Protein Translocation
    Sayem ASM, Arya A, Karimian H, Krishnasamy N, Ashok Hasamnis A, Hossain CF
    Molecules, 2018 Jan 28;23(2).
    PMID: 29382104 DOI: 10.3390/molecules23020258
    Diabetes is associated with obesity, generally accompanied by a chronic state of oxidative stress and redox imbalances which are implicated in the progression of micro- and macro-complications like heart disease, stroke, dementia, cancer, kidney failure and blindness. All these complications rise primarily due to consistent high blood glucose levels. Insulin and glucagon help to maintain the homeostasis of glucose and lipids through signaling cascades. Pancreatic hormones stimulate translocation of the glucose transporter isoform 4 (GLUT4) from an intracellular location to the cell surface and facilitate the rapid insulin-dependent storage of glucose in muscle and fat cells. Malfunction in glucose uptake mechanisms, primarily contribute to insulin resistance in type 2 diabetes. Plant secondary metabolites, commonly known as phytochemicals, are reported to have great benefits in the management of type 2 diabetes. The role of phytochemicals and their action on insulin signaling pathways through stimulation of GLUT4 translocation is crucial to understand the pathogenesis of this disease in the management process. This review will summarize the effects of phytochemicals and their action on insulin signaling pathways accelerating GLUT4 translocation based on the current literature.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  14. Comparison of oxidative damage in Malaysian end-stage renal disease patients with or without non-insulin-dependent diabetes mellitus
    Kuppusamy UR, Indran M, Ahmad T, Wong SW, Tan SY, Mahmood AA
    Clin Chim Acta, 2005 Jan;351(1-2):197-201.
    PMID: 15563890 DOI: 10.1016/j.cccn.2004.09.014
    BACKGROUND: Comparisons of oxidative indices and total antioxidant status between end-stage renal disease (ESRD) patients with or without diabetes is scant, especially in the Asian population.
    METHOD: The assays were carried out according to known established protocols.
    RESULT: The present study showed that ESRD patients with or without non-insulin-dependent diabetes mellitus (NIDDM) did not have any significant differences in antioxidant enzyme activities, advanced glycated end products (AGE), advanced oxidized protein products (AOPP) and ferric reducing ability of plasma (FRAP), indicating that hyperglycemia does not exacerbate oxidative damage in ESRD. The regulation of catalase and glutathione peroxidase is also altered in ESRD. Elevated FRAP was observed in both ESRD groups (with and without NIDDM). The dialysis process did not alter the antioxidant enzyme activities but decreased AGEs and FRAP and increased AOPP levels.
    CONCLUSION: Oxidative stress is present in ESRD but this is not significantly exacerbated by hyperglycemia. The contribution of components in the pathology of renal failure towards oxidative stress exceeds that of hyperglycemia.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology*
  15. Fulltext Morphometric analysis of skin microvasculature in the diabetic foot
    Yusof MI, Al-Astani AD, Jaafar H, Rashid FA
    Singapore Med J, 2008 Feb;49(2):100-4.
    PMID: 18301834
    INTRODUCTION: This study was designed to evaluate the histopathological features of skin microvasculature in patients with a diabetic foot, specifically the number of blood vessels, number of endothelial cells and endothelial thickness.
    METHODS: This study involved 41 diabetic foot patients admitted to Hospital Universiti Sains Malaysia for surgical management of foot problems. Skin biopsies were taken for histological evaluation following surgical procedures, such as wound debridement or local foot amputation. The skin microvasculature features examined were the number of blood vessels, the endothelial thickness of the vessels and the cross-sectional endothelial cell count. The findings were compared with the similar parameters of non-diabetic patients (control) and analysed.
    RESULTS: The mean blood vessel count (BVC), endothelial cell thickness (ECT) and endothelial cell count (ECC) for the diabetic group were 12.56 +/- 2.77, 4.81 +/- 1.5 micrometres and 7.07 +/- 1.88, respectively. The mean BVC, ECT and ECC for the non-diabetic control group were 5.25 +/- 1.98, 1.9 +/- 0.55 micrometres and 4.11 +/- 1.17, respectively. The mean BVC, ECT and ECC for the diabetic group were significantly higher than those for the non-diabetic control group.
    CONCLUSION: The increased number of blood vessels to the skin and their endothelial cell number and thickness may be the contributing factors for problems related to the diabetic foot, such as tendency for skin ulceration, infection and poor wound-healing in these patients. These may also contribute to secondary changes of diabetic foot lesions, indicating failure of adequate vascularisation of the foot.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  16. Increased risk of insulin resistance in rat offsprings exposed prenatally to white rice
    Imam MU, Ismail M, Ooi DJ, Sarega N, Ishaka A
    Mol Nutr Food Res, 2015 Jan;59(1):180-4.
    PMID: 25329877 DOI: 10.1002/mnfr.201400396
    White rice (WR) is a major staple food for people in developing countries and it may be responsible for the growing incidence of type 2 diabetes. Nonpregnant Female Sprague Dawley rats fed with WR or brown rice (BR) for 8 weeks were mated with age-matched male rats maintained on normal pellet over the same period. Offsprings were fed normal pellet after weaning until 8 weeks postdelivery. Rats fed with WR and their offsprings showed worsened oral glucose tolerance test, lower serum adiponectin levels, and higher weights, homeostatic model assessment of insulin resistance, serum retinol binding protein-4 levels, and leptin levels, compared with the normal and BR groups, suggesting an increased risk of insulin resistance. Furthermore, transcriptional levels of genes involved in insulin signaling showed different expression patterns in the liver, muscle, and adipose tissues of mothers and offsprings in both WR and BR groups. The results propose that the cycle of WR-induced insulin resistance in offsprings due to prenatal exposure, followed by their consumption of WR later in life may contribute to diabetes incidents. These findings are worth studying further.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  17. Reduced expression of prostacyclin synthase and nitric oxide synthase in subcutaneous arteries of type 2 diabetic patients
    Safiah Mokhtar S, M Vanhoutte P, W S Leung S, Imran Yusof M, Wan Sulaiman WA, Zaharil Mat Saad A, et al.
    Tohoku J. Exp. Med., 2013 11;231(3):217-22.
    PMID: 24225501
    Diabetic endothelial dysfunction is characterized by impaired endothelium-dependent relaxation. In this study, we measured the expression of endothelial nitric oxide synthase (eNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), prostacyclin synthase (PGIS), and prostacyclin receptor (IP) in subcutaneous arteries of type-2 diabetic and non-diabetic patients. Subcutaneous arteries were dissected from tissues from seven diabetics (4 males and 3 females) and seven non-diabetics (5 males and 2 females) aged between 18 to 65 years, who underwent lower limb surgical procedures. Diabetics had higher fasting blood glucose compared to non-diabetics, but there were no differences in blood pressure, body mass index and age. Patients were excluded if they had uncontrolled hypertension, previous myocardial infarction, coronary heart disease, renal or hepatic failure and tumor. The relative expression levels of eNOS, COX-1, COX-2, PGIS and IP receptor were determined by Western blotting analysis, normalized with the β-actin level. Increased expression of COX-2 was observed in subcutaneous arteries of diabetics compared to non-diabetics, whereas the expression levels of eNOS and PGIS were significantly lower in diabetics. There were no significant differences in expression levels of COX-1 and IP receptor between the two groups. Immunohistochemical study of subcutaneous arteries showed that the intensities of eNOS and PGIS staining were lower in diabetics, with higher COX-2 staining. In conclusion, type-2 diabetes is associated with higher COX-2 expression, but lower eNOS and PGIS expression in subcutaneous arteries. These alterations may lead to impaired endothelium-dependent vasodilatation, and thus these proteins may be potential targets for protection against the microvascular complications of diabetes.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  18. Pancreatic gene variants potentially associated with dipeptidyl peptidase-4 inhibitor treatment response in Type 2 diabetes
    Jamaluddin JL, Huri HZ, Vethakkan SR, Mustafa N
    Pharmacogenomics, 2014 Feb;15(2):235-49.
    PMID: 24444412 DOI: 10.2217/pgs.13.234
    In the adult pancreas, the expression of the genes PAX4, KCNQ1, TCF7L2, KCNJ11, ABCC8, MTNR1B and WFS1 are mainly restricted to β cells to maintain glucose homeostasis. We have identified these genes as the main regulators of incretin-mediated actions, and therefore they may potentially influence the response of DPP-4 inhibitors. This review represents the first detailed exploration of pancreatic β-cell genes and their variant mechanisms, which could potentially affect the response of DPP-4 inhibitors in Type 2 diabetes. We have focused on the signaling pathways of these genes to understand their roles in gastrointestinal incretin-mediated effects; and finally, we sought to associate gene mechanisms with their Type 2 diabetes risk variants to predict the responses of DPP-4 inhibitors for this disease.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
  19. Clinical predictors of non-diabetic renal disease and role of renal biopsy in diabetic patients with renal involvement: a single centre review
    Chong YB, Keng TC, Tan LP, Ng KP, Kong WY, Wong CM, et al.
    Ren Fail, 2012;34(3):323-8.
    PMID: 22250665 DOI: 10.3109/0886022X.2011.647302
    BACKGROUND:
    Type 2 diabetes mellitus (T2DM) is reportedly the leading cause of end-stage renal disease (ESRD) worldwide. However, non-diabetic renal diseases (NDRD) are not uncommon among T2DM patients with renal involvement. Our study aimed to examine the prevalence of NDRD in T2DM and clinical markers for diabetic nephropathy (DN) and NDRD and to determine the role of renal biopsy in T2DM patients and its impact on clinical practice.

    METHODS:
    We conducted a retrospective analysis of T2DM patients in whom renal biopsies were performed from January 2004 to March 2008 (n = 110).

    RESULTS:
    Biopsy results were divided into three groups: group I/pure DN (62.7%), group II/isolated NDRD (18.2%), and group III/mixed lesions (19.1%). The causes of NDRD in decreasing order of frequency were acute interstitial nephritis, glomerulonephritides, hypertensive renal disease, and acute tubular necrosis. Significant clinical markers for DN are presence of diabetic retinopathy and longer duration of diabetes. For NDRD, useful clinical markers include the presence of acute renal failure and microscopic hematuria. In the DN subgroup, Indians had significantly shorter duration of diabetes on biopsy compared with Malays and Chinese.

    CONCLUSIONS:
    NDRD is prevalent in T2DM patients, and given its potentially treatable nature, renal biopsy should be considered in T2DM patients with nephropathy, especially in those with atypical features.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology*
  20. Diabetes mellitus exacerbates advanced glycation end product accumulation in the veins of end-stage renal failure patients
    Nazratun N, Mahmood AA, Kuppusamy UR, Ahmad TS, Tan SY
    Vasc Med, 2006 Nov;11(4):245-50.
    PMID: 17390548
    The excess accumulation of advanced glycation end products (AGEs) contributes to the chronic complications of type 2 diabetes mellitus (DM) and renal failure. Biopsy specimens (n = 184) of arterial (n = 92) and venous (n = 92) tissues were obtained (radial artery and cephalic vein) from end-stage renal disease (ESRD) patients with or without DM and normal healthy subjects (n = 12) requiring surgery (trauma patients). Immunohistochemical assessment of the blood vessels revealed the presence of pentosidine (AGE marker) in both veins and arteries in 72% of the ESRD patients. The percentage of arteries and veins that showed positive pentosidine staining in ESRD patients with type 2 DM alone was 100% and 92% respectively, in the non-diabetic ESRD patients it was < 70% (for arteries and veins), and in the ESRD patients with hypertension as an additional co-morbidity to type 2 DM it was 70% and 82%, respectively. The veins of ESRD patients with DM showed a strong (+++) positive staining and very strong (++++) positive staining was observed in the patients with DM and hypertension. Only mild (+) or moderate (++) pentosidine staining intensity was observed in the arteries of ESRD patients without or with comorbidities, respectively. The accumulation of AGE in the vein rather than the artery may be a better reflection of the extent of complications of ESRD.
    Matched MeSH terms: Diabetes Mellitus, Type 2/pathology
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